Retinoic acid receptor beta enhanced the anti-cancer stem cells effect of beta-carotene by down-regulating expression of delta-like 1 homologue in human neuroblastoma cells
- 주제(키워드) beta-carotene , Neuroblastoma , Cancer stem cells , Retinoic acid beta , DLK1
- 등재 SCIE, SCOPUS
- 발행기관 ACADEMIC PRESS INC ELSEVIER SCIENCE
- 발행년도 2016
- URI http://www.dcollection.net/handler/ewha/000000139829
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bbrc.2016.10.041
초록/요약
Neuroblastoma (NB) is childhood malignancy that retains characteristics of cancer stem cells (CSCs). Targeting the CSCs is one of the therapeutic strategies proposed to achieve complete remission of NB. beta-carotene (BC), an active precursor of retinoids, is a well-known antioxidant reported to possess anti-CSCs effects. Here, we investigated the involvement of retinoic acid receptors (RARs) in the anti-CSCs effects of BC. Treatment with BC or retinoic acid (RA) upregulated RAR beta mRNA expression in two NB cell lines. Inhibition of RAR beta using siRNA up-regulated gene expression of delta-like 1 homologue (DLK1), a marker of CSCs. To understand the molecular mechanisms of RAR beta-mediated inhibition of DLK1, four retinoic acid receptor elements (RAREs) were identified in the promoter of DLK1. Chromatin immunoprecipitation assays indicated that RAR beta bound directly to a RARE in the DLK1 promoter region. Knock-down of RAR beta also increased the self-renewal capacity of NB cells, which was suppressed by BC. Taken together, this study provided evidence that the therapeutic anti-CSCs effects of BC depend on RAR beta and its ability to interact with and down-regulate the CSCs marker, DLK1. (C) 2016 Elsevier Inc. All rights reserved.
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